l-perhydroimidazo<1,5-c>thiazole-5,7-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: l-perhydroimidazo<1,5-c>thiazole-5,7-dione
• 英文别名: 1H-imidazo[1,5-c][1,3]thiazole-5,7(6H,7aH)-dione；3,7a-dihydro-1H-imidazo[1,5-c][1,3]thiazole-5,7-dione
• 化学式: C₅H₆N₂O₂S
• mdl: MFCD00729065
• 分子量: 158.181
• InChiKey: VSHNGALPNIMBCM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  74.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  l-perhydroimidazo<1,5-c>thiazole-5,7-dione 在 盐酸 、 sodium hydride 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 4.0h， 生成 6-{4-[(3,4-dihydro-2H-chromen-2-ylmethyl)amino]butyl}-1H-imidazo[1,5-c][1,3]thiazole-5,7(6H,7aH)-dione hydrochloride
  参考文献：
  名称：

  New Serotonin 5-HT_1A Receptor Agonists with Neuroprotective Effect against Ischemic Cell Damage

  摘要：

  We report the synthesis of new compounds 4 35 based on structural modifications of different moieties of previously described lead UCM-2550. The new nonpiperazine derivatives, representing second-generation agonists, were assessed for binding affinity, selectivity, and functional activity at the 5-HT1A receptor (5-HT1AR). Computational beta(2)-based homology models of the ligand receptor complexes were used to explain the observed structure affinity relationships. Selected candidates were also evaluated for their potential in vitro and in vivo neuroprotective properties. Interestingly, compound 26 (2-{6-[(3,4:-dihydro-2H-chromen-2-ylmethyl)amino]hexyl}-tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione) has been characterized as a high-affinity and potent 5-HT1AR agonist (K-i, = 5.9 nM, EC50 = 21.8 nM) and exhibits neuroprotective effect in neurotoxicity assays in primary cell cultures from rat hippocampus and in the MCAO model of focal cerebral ischemia in rats.

  DOI：

  10.1021/jm2007886
• 作为产物：
  描述：

  potassium cyanate 、 L-硫代脯氨酸 在 硫酸 作用下， 以 水 为溶剂， 以70%的产率得到l-perhydroimidazo<1,5-c>thiazole-5,7-dione
  参考文献：
  名称：

  Solution conformation and dynamics ofL-6-methylperhydroimidazo[1,5-c]thiazole-5,7-dione (γ-thiaprolinehydantoin). A1H and13C NMR study

  摘要：

  AbstractThe solution conformation of L‐6‐methylperhydroimidazo[1,5‐c]thiazole‐5,7‐dione (γ‐thiaprolinehydantoin) has been determined from an extensive 1H and 13C NMR study, allowing the extraction of vicinal inter‐proton and carbon‐hydrogen coupling constants. The major conformation of the thiazolidine ring is an envelope with C‐δ as the flap exo (δ−). In solution the preferred solid state (twist) conformer with C‐α exo and C‐β endo (αβT) is only a minor contributor. 13C spin–lattice relaxation data reveal the flexibility of the thiazolidine ring.

  DOI：

  10.1002/omr.1270210509

文献信息

• New Serotonin 5-HT_1A Receptor Agonists with Neuroprotective Effect against Ischemic Cell Damage
  作者：Isabel Marco、Margarita Valhondo、Mar Martı́n-Fontecha、Henar Vázquez-Villa、Joaquı́n Del Rı́o、Anna Planas、Onintza Sagredo、José A. Ramos、Iván R. Torrecillas、Leonardo Pardo、Diana Frechilla、Bellinda Benhamú、Marı́a L. López-Rodrı́guez

  DOI：10.1021/jm2007886

  日期：2011.12.8

  We report the synthesis of new compounds 4 35 based on structural modifications of different moieties of previously described lead UCM-2550. The new nonpiperazine derivatives, representing second-generation agonists, were assessed for binding affinity, selectivity, and functional activity at the 5-HT1A receptor (5-HT1AR). Computational beta(2)-based homology models of the ligand receptor complexes were used to explain the observed structure affinity relationships. Selected candidates were also evaluated for their potential in vitro and in vivo neuroprotective properties. Interestingly, compound 26 (2-6-[(3,4:-dihydro-2H-chromen-2-ylmethyl)amino]hexyl}-tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione) has been characterized as a high-affinity and potent 5-HT1AR agonist (K-i, = 5.9 nM, EC50 = 21.8 nM) and exhibits neuroprotective effect in neurotoxicity assays in primary cell cultures from rat hippocampus and in the MCAO model of focal cerebral ischemia in rats.
• Solution conformation and dynamics ofL-6-methylperhydroimidazo[1,5-c]thiazole-5,7-dione (γ-thiaprolinehydantoin). A1H and13C NMR study
  作者：Frans A. M. Borremans、Milos Buděšínský、Roland E. A. Callens、Marc J. O. Anteunis

  DOI：10.1002/omr.1270210509

  日期：1983.5

  AbstractThe solution conformation of L‐6‐methylperhydroimidazo[1,5‐c]thiazole‐5,7‐dione (γ‐thiaprolinehydantoin) has been determined from an extensive 1H and 13C NMR study, allowing the extraction of vicinal inter‐proton and carbon‐hydrogen coupling constants. The major conformation of the thiazolidine ring is an envelope with C‐δ as the flap exo (δ−). In solution the preferred solid state (twist) conformer with C‐α exo and C‐β endo (αβT) is only a minor contributor. 13C spin–lattice relaxation data reveal the flexibility of the thiazolidine ring.